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Published ahead of print on August 16, 2006
J Am Soc Nephrol 17: 2368-2382, 2006
© 2006 American Society of Nephrology
doi: 10.1681/ASN.2006060620
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Homer W. Smith Award Lecture

Acid-Base Transport by the Renal Proximal Tubule

Walter F. Boron

Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut

Address correspondence to: Dr. Walter F. Boron, Department of Cellular and Molecular Physiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520-8026. Phone: 203-785-4070; Fax: 203-785-4951; E-mail: walter.boron{at}yale.edu

One of the major tasks of the renal proximal tubule is to secrete acid into the tubule lumen, thereby reabsorbing approximately 80% of the filtered HCO3– as well as generating new HCO3– for regulating blood pH. This review summarizes the cellular and molecular events that underlie four major processes in HCO3– reabsorption. The first is CO2 entry across the apical membrane, which in large part occurs via a gas channel (aquaporin 1) and acidifies the cell. The second process is apical H+ secretion via Na-H exchange and H+ pumping, processes that can be studied using the NH4+ prepulse technique. The third process is the basolateral exit of HCO3– via the electrogenic Na/HCO3 co-transporter, which is the subject of at least 10 mutations that cause severe proximal renal tubule acidosis in humans. The final process is the regulation of overall HCO3– reabsorption by CO2 and HCO3– sensors at the basolateral membrane. Together, these processes ensure that the proximal tubule responds appropriately to acute acid-base disturbances and thereby contributes to the regulation of blood pH.




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